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10.26355/eurrev_201712_14006. transwell assays. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR\616\3p binds to TFPI2 mRNA. Results We established that TFPI2 protein levels were significantly upregulated in PE placental tissues. In addition, we found that miR\616\3p binds specifically to the 3\UTR region of TFPI2 mRNA. Furthermore, miR\616\3p knockdown or TFPI2 overexpression substantially impaired cell growth and migration, whereas miR\616\3p upregulation or TFPI2 knockdown stimulated cell proliferation and migration. This miR\616\3p/TFPI2 axis was also found to affect the epithelial\mesenchymal transition process in PE. Conclusions Our results demonstrated that TFPI2 plays a vital role in the progression of PE and might provide a prospective therapeutic strategy to mitigate the severity of the disorder. AbbreviationsmiRNAmicroRNAPEpreeclampsiaTFPI2tissue factor pathway inhibitor 2 1.?INTRODUCTION Preeclampsia (PE) is a pregnancy\specific syndrome characterized by gestational kidney disease involving glomerular endothelial injury. It induces severe clinical maternal hypertension and proteinuria.1 It has been reported that PE affects 2%\8% of pregnancies worldwide.2 When severe, uncontrolled symptoms of the disorder can result in significant morbidity and mortality of both mother and foetus. Pamidronate Disodium As would be expected, the disease induces a series of typical complications, including refractory hypertension, kidney damage and acute pulmonary oedema.3 Currently, preventative measures Pamidronate Disodium for the disorder include aspirin therapy, low\intake calcium supplementation and treatment of prior hypertension with medication.2, 4, 5. Despite these efforts, delivery of the baby and placenta remains the most effective treatment for patients with PE.6, 7 Though recent developments have improved its treatment, the disease mechanism still remains unclear. It has been reported that tissue factor pathway inhibitor 2 (TFPI2) may play a role in numerous biological behaviours, such as cell proliferation, differentiation and apoptosis.8, 9, 10 As a suppressor gene, TFPI2 is known to be dysregulated in multiple human disorders, including PE11 and various cancers.8, 10 Although the expression levels of TFPI2 have been characterized, the potential mechanisms of upregulated TFPI2 expression have not yet been explored, especially in severe cases Rabbit polyclonal to BMPR2 of PE. MicroRNAs (miRNAs) are a class of small and endogenous RNAs of 21\25 nucleotides (nts) in length.12, 13 A single miRNA can target multiple genes and several miRNAs can regulate the same gene. This complex network regulates the expression of multiple genes through a single miRNA. Several combinations of miRNAs can also serve to modulate the expression of a gene.14 MiRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri\miRNAs).15 It may play particularly important roles in restraining the main function of target gene by directly interacting with its mRNA 3?\untranslated region (3?\UTR), with transcriptional degradation/translational repression. Moreover, several mRNAs may have multiple binding sites for different miRNAs, resulting in a complex regulatory network.16 Altogether, miRNAs are known to be involved in many pathological and physiological processes, such as cellular growth, organogenesis, invasion, migration and apoptosis.17 The accumulated evidence suggests that the analysis of miRNAs will prove to be useful in studying a variety of diseases, ranging from diabetes18 to tumourgenesis.19, 20 Also, the study of miRNAs has expedited technological advancements in RNA\based Pamidronate Disodium treatments. MiRNAs are now being studied for their potential as next\generation drugs. A study of the miRNA expression profile in placentas of PE patients explored many PE\associated, differentially expressed miRNAs.21 To date, several studies have also revealed that miRNAs play a specific role in placental development and that more miRNAs could be candidates for biomarkers in early screening of PE.22, 23, 24 In this report, we established that the level of TFPI2 was significantly upregulated in PE placental tissues compared with.